ArticlePloS one2017
Yes1 signaling mediates the resistance to Trastuzumab/Lap atinib in breast cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- A phase 2 study of dasatinib in recurrent clear cell carcinoma of the ovary, fallopian tube, peritoneum or endometrium: NRG oncology/gynecologic oncology group study 0283.Gynecologic oncology · 2023Trial
- Identification of YES1 Inhibitors From Approved Drugs Using a Multimodal Deep Learning Framework.Molecular informatics · 2026Article
- Breast cancer genomic subtype-specific copy number alterations in metastases.Scientific reports · 2026Article
- Exploiting YES1-Driven EGFR Expression Improves the Efficacy of EGFR Inhibitors.Molecular cancer research : MCR · 2025Article
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- Neratinib plus dasatinib is highly synergistic in HER2-positive breast cancer in vitro and in vivo.Translational oncology · 2024Article
- ACSL3 regulates breast cancer progressionCancer biology & medicine · 2024Article
- YES1 as a potential target to overcome drug resistance in EGFR-deregulated non-small cell lung cancer.Archives of toxicology · 2024Article
- Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance.International journal of molecular sciences · 2024Review
- A renaissance for YES in cancer.Oncogene · 2023Review
- Role of YES1 signaling in tumor therapy resistance.Cancer innovation · 2023Review
- Targeting the Src N-terminal regulatory element in cancer.Oncotarget · 2023Article
- SRC Family Kinase Inhibition Targets YES1 and YAP1 as Primary Drivers of Lung Cancer and as Mediators of Acquired Resistance to ALK and Epidermal Growth Factor Receptor Inhibitors.JCO precision oncology · 2022Article
- The Human Tumor Atlas Network's beginning steps toward the future of collaborative multi-omic discovery.Cell reports. Medicine · 2022Article
- Identification of molecular subtypes and a six-gene risk model related to cuproptosis for triple negative breast cancer.Frontiers in genetics · 2022Article
- YES1 as a Therapeutic Target for HER2-Positive Breast Cancer after Trastuzumab and Trastuzumab-Emtansine (T-DM1) Resistance Development.International journal of molecular sciences · 2021Article
- Partial Response to Pyrotinib Plus Capecitabine in an Advanced Breast Cancer Patient withOncoTargets and therapy · 2021Article
- Overexpression of YES1 is associated with favorable prognosis and increased platinum-sensitivity in patients with epithelial ovarian cancer.Histology and histopathology · 2020Article
- YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers.Cancer science · 2020Article
- ERRα activates SHMT2 transcription to enhance the resistance of breast cancer to lapatinib via modulating the mitochondrial metabolic adaption.Bioscience reports · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundOverexpression of human epidermal growth factor receptor 2 (HER2) is observed in approximately 15-23% of breast cancers and these cancers are classified as HER2-positive breast cancer. Trastuzumab is the first-line targeted therapeutic drug for HER2-positive breast cancer and has improved patient overall survival. However, acquired resistance to trastuzumab is still a critical issue in breast cancer treatment. We previously established a trastuzumab-resistant breast cancer cell line (named as BT-474-R) from a trastuzumab-sensitive HER2-amplified cell line BT-474. Lapatinib is also a molecular-targeted drug for HER2-positive breast cancer, which acquired the resistance to trastuzumab. Acquired resistance to lapatinib is also an issue to be conquered.
methodsWe established trastuzumab/lapatinib-dual resistant cell line (named as BT-474-RL2) by additionally treating BT-474-R with lapatinib. We analyzed the mechanisms of resistance to trastuzumab and lapatinib. Besides, we analyzed the effect of the detected resistance mechanism in HER2-positive breast cancer patients.
resultsProto-oncogene tyrosine-protein kinase Yes1, which is one of the Src family members, was amplified, overexpressed and activated in BT-474-R and BT-474-RL2. Silencing of Yes1 by siRNA induced both BT-474-R and BT-474-RL2 to restore the sensitivity to trastuzumab and lapatinib. Pharmaceutical inhibition of Yes1 by the Src inhibitor dasatinib was also effective to restore the sensitivity to trastuzumab and lapatinib in the two resistant cell lines. Combination treatment with dasatinib and trastuzumab induced down-regulation of signaling molecules such as HER2 and Akt. Moreover, the combination treatments induced G1-phase cell-cycle arrest and apoptosis. Consistent with cell line data, high expression of Yes1 mRNA was correlated with worse prognosis in patients with HER2-positive breast cancer.
conclusionYes1 plays an important role in acquired resistance to trastuzumab and lapatinib in HER2-positive breast cancer. Our data suggest that pharmacological inhibition of Yes1 may be an effective strategy to overcome resistance to trastuzumab and lapatinib.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.